Incorporation of polyinosine-polycytidylic acid enhances cytotoxic T cell activity and antitumor effects by octaarginine-modified liposomes encapsulating antigen, but not by octaarginine-modified antigen complex

Int J Pharm. 2013 Jan 30;441(1-2):476-81. doi: 10.1016/j.ijpharm.2012.11.006. Epub 2012 Nov 16.


In a previous study, we reported on the efficient delivery of an antigen to the cytosol and a specific-antigen presentation on MHC class I in dendritic cells by rationally controlling the intracellular trafficking of ovalbumin (OVA), a model antigen, with stearylated octaarginine-modified liposomes (R8-Lip/OVA). However, no significant difference in antitumor effects against E.G7-OVA, OVA expressed lymphoma, was observed between R8-Lip/OVA and an electrostatic complex of R8 and OVA (R8/OVA-Com). In this study, we hypothesized that use of adjuvants clarified the difference in immune responses between R8-Lip/OVA and R8/OVA-Com, and selected polyinosine-polycytidylic acid (polyI:C) as an adjuvant. Cytotoxic T lymphocyte (CTL) activity of the polyI:C and OVA encapsulated R8-Lip (R8-Lip/PIC/OVA) was drastically enhanced compared to R8-Lip/OVA and complete Freund's adjuvant with OVA. Moreover, the incorporation of polyI:C clearly was critical for the difference in antitumor effects and CTL activities between R8-Lip/OVA and R8/OVA-Com. These findings suggest that the carriers that are incorporated polyI:C has a great influence on the induction of cellular immunity in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Cell Line, Tumor
  • Female
  • Freund's Adjuvant / pharmacology
  • Immunity, Cellular / immunology
  • Liposomes
  • Lymphoma / drug therapy*
  • Lymphoma / immunology
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Ovalbumin / administration & dosage*
  • Ovalbumin / immunology
  • Poly I-C / administration & dosage*
  • Poly I-C / pharmacology
  • Static Electricity
  • T-Lymphocytes, Cytotoxic / immunology


  • Adjuvants, Immunologic
  • Liposomes
  • Oligopeptides
  • octaarginine
  • Ovalbumin
  • Freund's Adjuvant
  • Poly I-C